Even without overt exocrine pancreatic dysfunction, diabetic cats produce amylin (an amyloid precursor) that is deposited in islet cells, leading to decreased insulin production. In humans, many of the genes associated with type 2 DM are associated with insulin secretion from islet β cells.23 Additionally, exocrine pancreatic disease occurs as a comorbidity with DM, and elevated feline pancreatic lipase immunoreactivity (fPLI) may be seen in diabetic cats.²⁴ Pancreatic diseases such as pancreatitis, pancreatic adenocarcinoma,²⁵ and genetic associations may also play a role.

Diabetes mellitus arises because of complex interactions of pancreatic and multiple peripheral factors. The most common peripheral factors are age, sex, and breed as well as obesity, diet, corticosteroid administration, and concurrent conditions. Epidemiologic studies in cats consistently show DM to be a disease of older cats, with an increased incidence in cats >8 years of age.1,3,4,9 An association of age with insulin resistance is controversial in people as studies have discordant results, most likely because of differences in overall health, physical training, and liver size.^26,27 Multiple studies have demonstrated increased insulin resistance in male cats (in particular after neutering) that is consistent with the overrepresentation of males among diabetic cats.^7,28,29

Several studies indicate that Burmese cats have a higher risk of DM than other cats in Australia, New Zealand, Europe, and the United Kingdom.^1,2,4,11 Breed predispositions are likely to be analogous to the situation for humans, wherein DM is more prevalent in some indigenous groups such as Aboriginal Australians, African Americans, and Pima Indians.^30–32 In humans, type 2 DM is a polygenic disease with complex inheritance; genetic variants account for <10% of overall risk while the effect of environment is more important. Studies have identified 20 common genetic variants associated with type 2 DM. Most of these genes are associated with regulation of insulin secretion from islet β cells in response to insulin resistance, but there are also genes related to glucose transport and insulin sensitivity. Many associated genes have unknown roles. In most cases, multiple genes are affected.³³

Research into genetic influences on DM in cats is at a preliminary stage. Several genetic loci associated with DM have been identified, such as loci associated with DM in lean cats³⁴ and genetic polymorphism in the melanocortin 4 receptor which is associated with DM in obese cats,³⁵ similar to humans. As well, one study found support for the hypothesis that inflammatory monocytes play a role in the pathogenesis of DM in cats, similar to what is seen in humans.³⁶ The increasing availability of genome-wide association studies will make searches for specific genes easier in cats, but the complex interactions of multiple genes in humans may make interpretation more difficult in cats, where the number of cases available for study will be far less than in studies of people.

Obesity has been directly related to insulin resistance in cats as well as humans^7,21 and is known to reduce GLUT4 expression.²¹ Other consequences of obesity in people, such as decreased insulin signaling and glucose disposal rates,¹³ are also likely to be relevant in cats. For obesity (and insulin resistance generally) to be associated with type 2 DM, the islet β cells must be unable to compensate fully for decreased insulin sensitivity.¹³ Weight loss is therefore an important component of diabetes management in cats as well as people.

In comparison to most mammals, cats have lower hepatic activity of the enzyme glucokinase, which plays the important role of a glucose sensor. Cats compensate by having elevated levels of glucose 6-phosphate. This altered glucose-sensing pathway in the feline liver may represent an evolutionary adaptation to a low-carbohydrate diet.¹⁵ These changes create challenges for any cat to handle the high glucose loads provided by high-carbohydrate diets and, if coupled with insulin resistance (from any cause), can result in DM. Studies have demonstrated improved remission rates when cats are fed low-carbohydrate, high-protein diets compared with high-fiber diets.^37–39

Specific infections in people (e.g., hepatitis C) have been correlated with insulin resistance,⁴⁰ although the reasons for the associations are not clear. Additionally, tumor necrosis factor-α, a cytokine involved in systemic inflammation and regulation of immune cells, plays a role in the pathophysiology of insulin resistance.⁴¹ Managing underlying infections is an important component of reducing insulin resistance. Azotemia associated with renal disease⁴² and hyperthyroidism,⁴³ both common diseases in older cats, also contributes to insulin resistance. Management of concurrent conditions is important in management of DM in cats.

Glucocorticoids impair insulin-dependent glucose uptake by peripheral cells and enhance hepatic gluconeogenesis as well as inhibit insulin secretion from islet β cells.⁴⁴ One study of 14 healthy cats given immunosuppressive oral doses of prednisolone (4.4 mg/kg/day) or dexamethasone (0.55 mg/kg/day) for 56 days found increased BG in all cats, but clinical signs were seen in only one cat (anorexia, icterus, pruritus, medial curling of the pinnae).⁴⁵ In a retrospective study, the records of 143 cats receiving prednisolone at >1.9 mg/kg/day for >3 weeks were evaluated.⁴⁶ Prednisolone-induced DM was diagnosed in 14 cats (9.7%); in most cases, DM developed within 3 months of starting therapy.

Catecholamines and other hormones released during stress states contribute to the development of hyperglycemia by directly stimulating glucose production and interfering with tissue disposal of glucose. In a normal individual, hyperglycemia stimulates secretion of insulin and inhibits secretion of glucagon, effects that will diminish the degree of hyperglycemia resulting from direct actions of stress hormones on glucose production and disposal. Cats with impaired islet β cell responses to glucose will be particularly prone to the development of marked hyperglycemia during stress states because they may be unable to respond with insulin secretion.⁴⁷

Chronic hyperglycemia itself suppresses the insulin response in three distinct ways:

A continuum exists in that the changes are reversible until a certain point in time.48

The upper limit for fasting BG concentration in normal cats is 6.3–6.5 mmol/L (113–117 mg/dL) in studies using a portable BG meter with whole blood and after overnight hospitalization with an 18–24 hour fast.49,50 Concentrations consistently above this should be considered pre-DM unless overt DM is confirmed (see later).

Elevations of BG above the renal threshold (>14–16 mmol/L [>250–290 mg/dL]) result in glucosuria, which is part of the diagnostic criteria. Urine specific gravity may be dilute and associated with PD; however, some diabetic cats have concentrated urine. One in vitro study showed that addition of substantial amounts of glucose to canine and feline urine samples had only minimal effect on specific gravity.⁵¹ Studies have shown that 12%–13% of cats with DM have a urinary tract infection.^52,53 However, there are few indications to culture urine when patients have no lower urinary tract signs because treatment of subclinical bacteriuria is not indicated, even in patients with comorbidities such as DM.⁵⁴ This recommendation is based on human medicine where treatment of asymptomatic bacteriuria in patients with most comorbidities, including endocrinopathies, is not recommended.

Evidence of gluconeogenesis (ketosis or ketonuria) supports a diagnosis of DM.25 All diabetic cats in one study had at least some elevation of the plasma ketone, beta-hydroxybutyrate (BHB).⁵⁵ Using a plasma BHB value of 0.22 mmol/L as the cutoff for diagnosis of DM, the false positive rate was 9%. Increasing the cutoff value to 0.58 mmol/L reduced the false positive rate to 1.2%. No cat with moderate or severe stress-related hyperglycemia had BHB concentrations >0.22 mmol/L.

Glycosylated proteins useful in the diagnosis of DM include fructosamine and glycosylated hemoglobin (GHb). Fructosamine concentration must be used carefully because in cats a single measurement most likely reflects the mean BG concentration for about the past week (it is longer in other species).⁵⁶ Further, fructosamine may not exceed the reference range in cats with moderate hyperglycemia (<17 mmol/L [<306 mg/dL]);⁵⁶ serial BG testing is more reliable in those cases. Most cats with newly diagnosed DM will have fructosamine levels >400 µmol/L.⁵⁷ However, fructosamine can be suppressed to within the reference range in cats with concurrent uncontrolled hyperthyroidism.⁵⁸

Several studies have evaluated GHb concentrations in diabetic cats.^59–62 Similar to fructosamine, mean GHb concentrations are higher in untreated diabetic cats compared to healthy cats and higher in poorly controlled than well-controlled diabetics. Further, GHb concentrations decline with improved glycemic ­control. However, there is overlap in GHb concentrations between well-controlled and poorly controlled diabetic cats which may be due to duration of the disease or duration of good or poor glycemic control. Commercial tests for A1C, commonly used to monitor DM in humans, are becoming available for cats and dogs but more studies are needed, especially to validate assays for veterinary use.

Routine biochemistry changes in DM are variable but commonly include elevations in the hepatic enzymes, alanine aminotransferase (ALT) and alkaline phosphatase (ALP). These values should return to normal with successful management of DM. If ALT or ALP concentrations remain elevated in a well-controlled diabetic cat, another cause for the increase should be investigated.

A complete blood count is typically normal, but a stress leukogram with mild neutrophilia and lymphopenia may be seen. Concurrent infection can cause a more pronounced neutrophilia, perhaps with a left shift.

Mild hyperglycemia can be caused by stress (e.g., travel to the clinic, restraint) or concurrent illness. Concurrent medical conditions should be identified and treated before further BG testing is performed, especially if clinical signs of DM are absent. When blood is sampled shortly after arrival at a veterinary clinic, a normal screening BG should be <9.2 mmol/L (<166 mg/dL) to allow for the effects of stress. Cats are capable of increasing BG concentrations markedly within minutes of a stressor.63 Indeed, in one study, stress-induced hyperglycemia was reportedly as high as 60.4 mmol/L (1087 mg/dL).⁶⁴ In some cats, the peak BG concentration will not return to normal for hours after a stressor.⁶³ The authors of a study of 120 clinically normal cats 8 years of age and older recommend that senior cats with a screening BG concentration 6.5 to 10.5 mmol/L (117 to 189 mg/dL) should be retested several hours later.⁶⁵ Further, they recommend senior cats with an initial screening BG value >10.5 mmol/L (>189 mg/dL), or a second screening BG value >6.4 mmol/L (>116 mg/dL) several hours after the first, should be hospitalized overnight with an 18–24 hour fast and have fasting BG and glucose tolerance measured the next day. The same approach can be applied to cats >4 years of age with risk factors (e.g., obesity, chronic corticosteroid therapy, chronic pancreatitis, or a predisposed breed).⁶⁶

Fructosamine concentration is related to BG concentration. In many cases, serum fructosamine will be normal in cats with stress hyperglycemia. However, fructosamine should not be used to differentiate stress hyperglycemia from DM when the BG concentration is <20 mmol/L (<360 mg/dL).⁶⁶ In those cases, differentiation should be based on further BG testing and clinical signs. Transient hyperglycemia does not affect GHb results in nondiabetic and diabetic cats.⁵⁹

Currently, there is no definition of prediabetes in cats. To develop a definition of prediabetes based on measurements of glycosylated proteins, standardization of reference ranges for fructosamine and GHb across laboratories is needed. Also reference ranges based on sex should be developed for fructosamine as male cats tend to have higher values than females.67 Once reference ranges for glycosylated proteins have improved, research will be required to determine if these parameters are sensitive enough to detect prediabetes in cats.

Nurses/technicians can train owners to give insulin injections and explain what to do if a problem occurs ( e-Box 27.2). For example, if some of the insulin dose is spilled during injection, the owner should be warned not to give additional insulin to avoid overdose. Owners also need to be aware of the correct syringe size for the insulin prescribed and how to use an insulin pen if one is recommended. Nurses and technicians can also help owners learn how to perform home BG monitoring (HBGM). All members of the cat’s household should be aware of the clinical signs of hypoglycemia and what to do if it occurs. Close contact with owners during the initial weeks of insulin therapy can help identify and correct problems or misconceptions.

The amount of information owners receive upon a pet’s diagnosis of DM can be overwhelming. Some owners may need more time than others to adjust to changes in their own lifestyle. The veterinary team should avoid overburdening owners in the early weeks after diagnosis. It may be necessary to introduce the most important information first (e.g., how to measure and dose insulin, signs of hypoglycemia) and gradually add further information (e.g., performing HBGM) in the following weeks. It is also important for owners that perform HBGM to know they should never increase or decrease the insulin dose or frequency without consulting the veterinarian or nurse/technician.

The nurse/technician can also confirm that the owner has understood the information provided by the veterinarian and answer questions. This type of service can also help when owners have found information on the Internet that might contradict what they have been told by the veterinarian or that may be about inappropriate or dangerous treatments. Many veterinary clinics find it useful to curate a collection of reliable information sources (including videos) on topics such as DM that can be accessed by the owner on the practice website or that can be put into a handout.

Information prescriptions may be a useful approach for guiding owners when exploring information found online.^68,69 They were first devised to help human health care providers guide patients to reliable, understandable, up-to-date information about diseases. An information prescription should be specific to a disease or condition and contain links to reliable internet content (e.g., websites, videos, podcasts). The document can be personalized by adding the date and patient’s name and by the signature of the veterinarian or nurse/technician. An example is found in e-Box 27.3.

There is considerable room for improvement in educating and supporting owners. In an Internet survey of 748 owners of diabetic cats, only 49% were supervised by a veterinarian or nurse/technician while first handling and injecting insulin.⁷⁰ Less than half of veterinarians discussed how to recognize problems with regulation or HBGM. Most owners (71%) were using HBGM, suggesting they found other sources of instruction than the veterinary hospital. In fact, most owners (76%) found websites on their own to learn more about DM.

Quality of life (QOL) is important for both cat and owner. Owners that perceive treatment will have a negative impact on QOL may be more likely to choose euthanasia. One survey of 1192 veterinarians suggested that 1 in 10 diabetic pets are euthanized at the time of diagnosis and a further 1 in 10 are euthanized within 1 year due to lack of treatment success.71 The most important factors relating to the euthanasia decision were concurrent diseases, cost of treatment, age of the pet, difficulty controlling the disease, and impact on QOL for pet and owner. Diabetic cats in Canada (odds ratio [OR] 2.7), Australia (OR 2.3), and those in rural (OR 1.6) and mixed animal (OR 1.7) practices were more likely to be euthanized because of the diagnosis. Cats presented to referral hospitals were less likely to be euthanized (OR 0.6) than those seen in general practices. It is important to recognize that owners using referral hospitals are likely to be more motivated so the lower OR for euthanasia is not necessarily due to differences in DM management. The authors concluded there may be a benefit to improved owner education about DM and an emphasis on offering a choice of treatment styles based on intensiveness and cost.

A survey of 834 owners of diabetic dogs and cats in the United States was designed to report owner experiences and satisfaction in treating a diabetic pet.⁷² More cat (66%) than dog (50%) owners were satisfied with the level of diabetic control achieved for the pet. Cat owners were more likely than dog owners to use HBGM. Most owners felt treatment was expensive.

Using QOL tools may be helpful for adjusting the treatment style to the needs of the owner and managing owner expectations and fears. A QOL tool for diabetic cats with 29 questions centered on both owner and animal has been developed and validated.⁷³ The tool was tested with 221 owners of diabetic cats predominantly in the United States and the United Kingdom; about half of the owners performed HBGM. Nine of the top ten items judged by owners to have a negative impact were related to their own QOL rather than the cat’s QOL. Concerns included difficulty boarding the cat, difficulty leaving the cat with family or friends, worry about the disease, worry about hypoglycemia, and changes to work and social life. Identifying owner concerns and fears at the start of treatment can help the veterinary team provide tailored information and support.

If peripheral insulin resistance factors can be overcome, the diabetic cat may eventually be weaned from insulin if the islet β cells have not suffered irreversible damage from chronic glucotoxicity. With early intervention and good glycemic control, diabetic remission was achieved in 84% to 100% of cats in two studies.74,75 However, approximately 25%–30% of cats in remission will relapse, and <25% of those cats achieve remission a second time.^75,76 Loss of control of peripheral factors such as a return to a high-carbohydrate diet, recurrence of obesity, or development of azotemia may result in a return to an insulin-dependent state. It is important for owners to understand that diabetic remission does not mean cure. Remission may not be permanent, and the cat should still be considered diabetic (although not insulin dependent) and continue to receive appropriate care and monitoring.

Several studies have looked at factors associated with an increased chance of achieving remission. In one Internet survey of owners of diabetic cats treated with glargine insulin, strict glycemic control, administration of glucocorticoids before diagnosis, and absence of polyneuropathy were associated with likelihood of remission.⁷⁵ Factors that were not useful predictors of remission included age, sex, body weight, and presence of chronic kidney disease or hyperthyroidism. Cats that achieved remission had a lower mean maximum insulin dose (0.43 U/kg, every 12 hours) than cats that did not achieve remission (0.66 U/kg, every 12 hours).

In a study of 90 newly diagnosed diabetic cats, 50% achieved remission after a median of 48 days.⁷⁶ Insulin glargine was used for 47% of cats and protamine zinc insulin (PZI) for 53%. The median duration of remission was 151 days for cats still alive at the end of the study. Insulin was resumed in 29% of cats that had achieved remission, but six of the cats achieving remission did not require insulin again for more than 1000 days. In this study, age and cholesterol levels were predictive of remission in multivariate analysis. Increased serum cholesterol decreased the chance of remission by about 65%. For each year of age, the chance of remission increased by approximately 25%, suggesting that older cats may have slower disease progression. Duration of remission was longer with higher body weight and shorter with higher BG. Cats treated with glargine insulin had an increased chance of remission based on univariate analysis. Another study found remission was five times more likely for cats managed with the goal of near euglycemia (BG 3.3–8.8 mmol/L [59–158 mg/dL]) compared to cats managed by monitoring clinical signs.⁷⁷

Overall, studies suggest remission is most likely in the newly diagnosed diabetic cat managed with a long-acting insulin with the goal of tight glycemic control, fed a diabetes therapeutic diet, and monitored with frequent BG evaluations (whether in hospital or at home) to adjust insulin dosage. However, it must be noted that most studies have small numbers of cats, are not blinded to treatment, are of short duration, and may rely on owner interpretations.

A newer study of 185 client-owned cats that were followed until death, lost to follow-up, or the end of the 11-year study found the probability of remission was 56%.⁷⁸ Factors associated with likelihood of remission were recent prediabetic glucocorticoid use, lower mean BG during treatment, and lower mean insulin dose. Survival time ranged from 0 to 3808 days, with a median of 1488 days. Factors associated with increased survival time were a low-carbohydrate diet, achieving remission, lack of ketoacidosis at diagnosis, lower mean BG during treatment, and lower BG at diagnosis. Interestingly, the cats in this study were primarily treated by basing insulin requirements on clinical response, not BG measurements. This study shows that good outcomes can be achieved in diabetic cats without tight glycemic control based on BG measurements if other important components of treatment are provided.

As of this writing, the insulin types most often used in cats are (Table 27.1):

Table 27.1

Characteristics of Insulins Commonly Used to Treat Feline Diabetes Mellitus.

Insulin	Licensed for cats in Some Countries	Formulation	Action	Starting Dose (based on lean body weight)	Median Maintenance Dose
ProZinc (Boehringer Ingelheim)	Yes	U40; recombinant protamine zinc insulin	Long acting; Nadir 5–7 hours; Duration 12–24 hours Only gold members can continue reading. Log In or Register to continue Share this: Click to share on Twitter (Opens in new window) Click to share on Facebook (Opens in new window) Related Related posts: page Nutrition for the Normal Cat Feline Zoonotic Diseases and Prevention of Transmission Male Cats: Normal Reproduction, Reproductive Diseases and Conditions Stay updated, free articles. Join our Telegram channel Join Tags: The Cat Clinical Medicine and Management 2e Mar 30, 2025 | Posted by admin in GENERAL | Comments Off on Endocrinology Full access? Get Clinical Tree Get Clinical Tree app for offline access Get Clinical Tree app for offline access